681 research outputs found
Ectoplasm with an Edge
The construction of supersymmetric invariant actions on a spacetime manifold
with a boundary is carried out using the "ectoplasm" formalism for the
construction of closed forms in superspace. Non-trivial actions are obtained
from the pull-backs to the bosonic bodies of closed but non-exact forms in
superspace; finding supersymmetric invariants thus becomes a cohomology
problem. For a spacetime with a boundary, the appropriate mathematical language
changes to relative cohomology, which we use to give a general formulation of
off-shell supersymmetric invariants in the presence of boundaries. We also
relate this construction to the superembedding formalism for the construction
of brane actions, and we give examples with bulk spacetimes of dimension 3, 4
and 5. The closed superform in the 5D example needs to be constructed as a
Chern-Simons type of invariant, obtained from a closed 6-form displaying Weil
triviality.Comment: 25 page
Realizing the promise of population biobanks: a new model for translation
The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource for both clinical and public health practice, their potentiating ontology—that their outputs are perpetually a promise of scientific knowledge generation—renders translation rather less straightforward than drug discovery and treatment implementation. Biobanking science, therefore, provides a perfect counterpoint against which to test the bounds of translational research. We argue that translational research is a contextual and cumulative process: one that is necessarily dynamic and interactive and involves multiple actors. We propose a new multidimensional model of translational research which enables us to imagine a new paradigm: one that takes us from bench to bedside to backyard and beyond, that is, attentive to the social and political context of translational science, and is cognisant of all the players in that process be they researchers, health professionals, policy makers, industry representatives, members of the public or research participants, amongst others
Genomic markers to tailor treatments: waiting or initiating?
The decade since the publication of the Human Genome Project draft has ended with the discovery of hundreds of genomic markers related to diseases and phenotypes. However, the project has not yet delivered on its promise to tailor treatments for individuals. The number of genomic markers in clinical practice is very small. The number of markers to guide treatment decisions is even smaller. In order to speed up discovery and validation of genomic treatment selection markers, we call for considering the brilliant potential of randomized clinical trials. If biomedical research community can collaborate in organizing large-scale consortium of clinical trials associated with well-designed biobanks, these studies would soon act as huge laboratories for investigating genomic medicine; a big step forward towards personalizing medicine
Malaria-related mortality based on verbal autopsy in an area of low endemicity in a predominantly rural population in Ethiopia
<p>Abstract</p> <p>Background</p> <p>Although malaria is one of the most important causes of death in Ethiopia, measuring the magnitude of malaria-attributed deaths at community level poses a considerable difficulty. Nevertheless, despite its low sensitivity and specificity, verbal autopsy (VA) has been the most important technique to determine malaria-specific cause of death for community-based studies. The present study was undertaken to assess the magnitude of malaria mortality in a predominantly rural population of Ethiopia using VA technique at Butajira Rural Health Programme (BRHP) Demographic Surveillance Site (DSS).</p> <p>Methods</p> <p>A verbal autopsy was carried out for a year from August 2003 to July 2004 for all deaths identified at BRPH-DSS. Two trained physicians independently reviewed each VA questionnaire and indicated the most likely causes of death. Finally, all malaria related deaths were identified and used for analysis.</p> <p>Results</p> <p>A verbal autopsy study was successfully conducted in 325 deaths, of which 42 (13%) were attributed to malaria. The majority of malaria deaths (47.6%) were from the rural lowlands compared to those that occurred in the rural highlands (31%) and urban (21.4%) areas. The proportional mortality attributable to malaria was not statistically significant among the specific age groups and ecological zones. Mortality from malaria was reckoned to be seasonal; 57% occurred during a three-month period at the end of the rainy season between September and November. About 71% of the deceased received some form of treatment before death, while 12 (28.6%) of those who died neither sought care from a traditional healer nor were taken to a conventional health facility before death. Of those who sought treatment, 53.3% were first taken to a private clinic, 40% sought care from public health facilities, and the remaining two (6.7%) received traditional medicine. Only 11.9% of the total malaria-related deaths received some sort of treatment within 24h after the onset of illness.</p> <p>Conclusion</p> <p>The results of this study suggest that malaria plays a considerable role as a cause of death in the study area. Further data on malaria mortality with a relatively large sample size for at least two years will be needed to substantially describe the burden of malaria mortality in the study area.</p
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
Heritability and major gene effects on left ventricular mass in the Chinese population: a family study
BACKGROUND: Genetic components controlling for echocardiographically determined left ventricular (LV) mass are still unclear in the Chinese population. METHODS: We conducted a family study from the Chin-San community, Taiwan, and a total of 368 families, 1145 subjects, were recruited to undergo echocardiography to measure LV mass. Commingling analysis, familial correlation, and complex segregation analysis were applied to detect component distributions and the mode of inheritance. RESULTS: The two-component distribution model was the best-fitting model to describe the distribution of LV mass. The highest familial correlation coefficients were mother-son (0.379, P < .0001) and father-son (0.356, P < .0001). Genetic heritability (h(2)) of LV mass was estimated as 0.268 ± 0.061 (P < .0001); it decreased to 0.153 ± 0.052 (P = .0009) after systolic blood pressure adjustment. Major gene effects with polygenic components were the best-fitting model to explain the inheritance mode of LV mass. The estimated allele frequency of the gene was 0.089. CONCLUSION: There were significant familial correlations, heritability and a major gene effect on LV mass in the population-based families
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Mitochondrial Membrane Potential in Human Neutrophils Is Maintained by Complex III Activity in the Absence of Supercomplex Organisation
textabstractBackground: Neutrophils depend mainly on glycolysis for their enegry provision. Their mitochondria maintain a membrace potential (ΔΨm), which is usually generated by the repiratory chain complexes. We investigated the source of ΔΨm in neutrophils, as compared to peripheral blood mononuclear leukocytes and HL-60 cells, and whether neutrophils can still utilise this ΔΨm for the generation of ATP. Methods and Principal Findings: Individual activity of the oxidative phosphorylation complexes was significantly reduced in neutrophils, except for complex II and V, but ΔΨm was still decreased byinhibition of complex III, confirming the role of the respiratory chain in maintaining ΔΨm. Complex V did not maintain ΔΨm by consumption of ATP, as has previously been suggested for eosinophils shuttle. Furthermore, respiratory supercomplexes, which contribute to efficient coupling of the respiratory chain to ATP synthesis, were ladding in neutrophil mitochondria. When HL-60 cells were differentiated to neutrophil-like cells, they lost mitochondrial supercimplex organisation while gaining increased aerobic glycolysis, just like neutrophils. Conclusions: We show that neutrophils can maintain ΔΨm via the glycerol-3-phosphate shuttle, wereby their mitochondria play an important role in the regulation of aerobic glycolysis, rather than producing energy themselves. This peculiar mitochondrial phenotype is acquired during differentiation from myeloid precursors
Assessing causal relationships in genomics: From Bradford-Hill criteria to complex gene-environment interactions and directed acyclic graphs
Observational studies of human health and disease (basic, clinical and epidemiological) are vulnerable to methodological problems -such as selection bias and confounding- that make causal inferences problematic. Gene-disease associations are no exception, as they are commonly investigated using observational designs. A rich body of knowledge exists in medicine and epidemiology on the assessment of causal relationships involving personal and environmental causes of disease; it includes seminal causal criteria developed by Austin Bradford Hill and more recently applied directed acyclic graphs (DAGs). However, such knowledge has seldom been applied to assess causal relationships in clinical genetics and genomics, even in studies aimed at making inferences relevant for human health. Conversely, incorporating genetic causal knowledge into clinical and epidemiological causal reasoning is still a largely unexplored area
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